Radiotherapy (RT) is a frequent treatment modality for cancer patients. The goal of RT is to deliver a cytotoxic dose to the tumor, while minimizing the radiation exposure to the surrounding normal tissues. However, radiation pneumonitis is a serious and potentially lethal treatment-related complication of RT, and RT-induced pneumonitis is one of the most serious dose-limiting toxicities, particularly for patients receiving RT for lung cancer. The incidence of symptomatic radiation pneumonitis ranges from roughly 10% to 30% with radiotherapy or chemoradiotherapy (Robnett T J et al. (2000) Int J Radiat Oncol Biol Phys Vol. 48, pp 89-94; Seppenwoolde Y et al. (2003) Int J Radiat Oncol Biol Phys Vol. 55, pp 724-735). Symptoms of pneumonitis generally do not appear until at least 1 to 3 months after the completion of treatment. Late fibrosis might also develop months to years post-therapy. Lung fibrosis is the permanent scarring of lung tissue that occurs more gradually (over months to years) in response to the initial tissue injury and leads to permanent impairment of oxygen transfer. Chemotherapy administered with RT is expected to provide systemic control as well as to enhance loco-regional control via radiation sensitization. While the benefit of this combination therapy has been supported by several studies [Dillman, et al. (1996) J Natl. Cancer Inst. Vol. 88, pp 1210-1215; Furuse, et al. (1999) J. Clin. Oncol. Vol. 17, pp 2692-2699], it is unfortunately achieved at the expense of increased acute normal tissue toxicity [Byhardt, et al. (1998) Int. J. Radiat. Oncol. Biol. Phys. Vol. 42, pp 469-478; Bradley, et al. (2005) Int. J. Radiat. Oncol. Biol. Phys. Vol. 61, pp 318-328].
At present, no generally accepted method is available to predict an individual's risk of developing radiation pneumonitis. Therefore, there is a need for a method of determining whether a cancer patient is likely to be susceptible to radiation pneumonitis. Such a method would facilitate treatment modifications to minimize the extent of radiation injury as well as to offer possible early radiation pneumonitis preventive intervention.